1. Technical Field of the Invention
The present invention relates to novel compositions in the form of anhydrous unguents containing no petroleum jelly, in particular for topical application, comprising a vitamin D derivative optionally combined with an active agent of the family of steroidal anti-inflammatory agents.
2. Description of Background and/or Related and/or Prior Art
Vitamin D and its derivatives are generally administered in dermatology in the treatment of psoriasis because they limit the excessive production of skin cells on the affected surfaces and have proven advantageous for the treatment of this condition which is characterized, in particular, by the presence of thick, squamous and dry lesions.
It is known that a number of active ingredients having an advantageous therapeutic activity are sensitive to oxidation and undergo chemical degradation leading to a substantial loss of their activity in the presence of water.
In particular, vitamin D or certain vitamin D derivatives are unstable in an acidic environment (they exhibit maximum stability at pH values in the region of 8).
Furthermore, it is advantageous to administer several classes of active ingredients, in particular for the treatment of dermatological pathologies. This also makes it possible to increase the efficacy of the active ingredients and to reduce their toxicity (Cunliffe W. J., J. Dermato. Treat., 2000, 11 (suppl. 2) S13-S14). Here again, a problem of long-term chemical stability is frequently encountered during the formulation of two active agents in the same vehicle. This is in particular the case for the combination of a vitamin D derivative with a corticoid. Indeed, certain corticosteroids are unstable in a basic environment (they exhibit maximum stability at a pH of about 4 to 6). This combination is nevertheless advantageous in the treatment of psoriasis.
Consequently, in the case of a combination, it is advisable to formulate the combination of vitamin D or of a vitamin D derivative with an active agent of the family of steroidal anti-inflammatory agents in compositions of the anhydrous type.
The currently commercially available anhydrous compositions, allowing the formulation of water-sensitive active ingredients, while providing them with good chemical stability, are generally unguent-type compositions consisting mainly of petroleum jelly. However, the use of petroleum jelly is not satisfactory for the following reasons:
after application, certain compositions comprising petroleum jelly are felt to be sticky and greasy, and are furthermore shiny. The fatty residue left on the skin prevents patients with psoriasis from putting their clothes back on after treatment without the risk of leaving greasy marks on them, which does not necessarily encourage patients to follow their treatment. Noncompliance with the prescribed treatment is one of the main causes of failure: the article “Patients with psoriasis and their compliance with medication, Richards et al, J. Am. Acad Dermatol., October 1999, p. 581-583” states that nearly 40% of patients with a chronic disease such as psoriasis do not follow their treatment. The characteristics of the vehicle used in the pharmaceutical compositions are directly linked to the patient's compliance with their treatment;
moreover, the formulation of compositions in the form of petroleum jelly-based unguents requires compounds and specific conditions. Indeed, petroleum jelly is solid at room temperature, and has a melting point greater than 40° C. To be able to mix it with other compounds, it is necessary to formulate it in the liquid state, and therefore to produce the compositions at temperatures greater than 40° C. This is in particular the case described in WO2006/005842. However, such a method has as a disadvantage the formation of a phenomenon of encrusting. Indeed, the more rapid cooling of the outside of the composition compared with its center causes its abnormal hardening (encrusting), which has the effect of slowing, or even preventing, a perfect homogenization;
finally, the formulation of vitamin D derivatives, in particular of calcitriol, and of corticoids, in particular clobetasol, is delicate because of the sensitivity of these active agents to heat.